The purpose of the study was to examine (1) how patient adherence and eye drop technique were associated with visual field defect severity and (2) how general glaucoma adherence self-efficacy and eye ...drop technique self-efficacy were related to visual field defect severity.
Cross-sectional study conducted at a single private practice site.
Patients using eye drops for their glaucoma.
Subject adherence to glaucoma medications through Medication Events Monitoring System (MEMS) devices were measured, and eye drop instillation technique was assessed by video recording. General glaucoma medication adherence self-efficacy was measured using a 10-item scale, and eye drop technique self-efficacy was measured using a 6-item scale. Multivariate logistic regression was used to analyze the data.
Visual field defect severity.
Patients who were less than 80% adherent according to the MEMS devices were significantly more likely to have worse defect severity. Patients with lower scores on the general glaucoma medication adherence self-efficacy scale also were significantly more likely to have worse defect severity. Eye drop technique and eye drop technique self-efficacy were not related significantly to visual field defect severity.
Eye care providers need to assess patient adherence and to work with those patients with poor adherence to find ways to improve their ability and self-efficacy in using their glaucoma medications.
Proprietary or commercial disclosure may be found after the references.
Myocardial infarction (MI) elicits massive inflammatory leukocyte recruitment to the heart. Here, we hypothesized that excessive leukocyte invasion leads to heart failure and death during acute ...myocardial ischemia. We found that shortly and transiently after onset of ischemia, human and mouse cardiac fibroblasts produce granulocyte/macrophage colony-stimulating factor (GM-CSF) that acts locally and distally to generate and recruit inflammatory and proteolytic cells. In the heart, fibroblast-derived GM-CSF alerts its neighboring myeloid cells to attract neutrophils and monocytes. The growth factor also reaches the bone marrow, where it stimulates a distinct myeloid-biased progenitor subset. Consequently, hearts of mice deficient in either GM-CSF or its receptor recruit fewer leukocytes and function relatively well, whereas mice producing GM-CSF can succumb from left ventricular rupture, a complication mitigated by anti-GM-CSF therapy. These results identify GM-CSF as both a key contributor to the pathogenesis of MI and a potential therapeutic target, bolstering the idea that GM-CSF is a major orchestrator of the leukocyte supply chain during inflammation.
Objectives
The objective was to review and update key definitions and metrics for emergency department (ED) performance and operations.
Methods
Forty‐five emergency medicine leaders convened for the ...Third Performance Measures and Benchmarking Summit held in Las Vegas, February 21–22, 2014. Prior to arrival, attendees were assigned to workgroups to review, revise, and update the definitions and vocabulary being used to communicate about ED performance and operations. They were provided with the prior definitions of those consensus summits that were published in 2006 and 2010. Other published definitions from key stakeholders in emergency medicine and health care were also reviewed and circulated. At the summit, key terminology and metrics were discussed and debated. Workgroups communicated online, via teleconference, and finally in a face‐to‐face meeting to reach consensus regarding their recommendations. Recommendations were then posted and open to a 30‐day comment period. Participants then reanalyzed the recommendations, and modifications were made based on consensus.
Results
A comprehensive dictionary of ED terminology related to ED performance and operation was developed. This article includes definitions of operating characteristics and internal and external factors relevant to the stratification and categorization of EDs. Time stamps, time intervals, and measures of utilization were defined. Definitions of processes and staffing measures are also presented. Definitions were harmonized with performance measures put forth by the Centers for Medicare and Medicaid Services (CMS) for consistency.
Conclusions
Standardized definitions are necessary to improve the comparability of EDs nationally for operations research and practice. More importantly, clear precise definitions describing ED operations are needed for incentive‐based pay‐for‐performance models like those developed by CMS. This document provides a common language for front‐line practitioners, managers, health policymakers, and researchers.
We have shown that the aged microenvironment increases melanoma metastasis, and decreases response to targeted therapy, and here we queried response to anti-PD1.
We analyzed the relationship between ...age, response to anti-PD1, and prior therapy in 538 patients. We used mouse models of melanoma, to analyze the intratumoral immune microenvironment in young versus aged mice and confirmed our findings in human melanoma biopsies.
Patients over the age of 60 responded more efficiently to anti-PD-1, and likelihood of response to anti-PD-1 increased with age, even when we controlled for prior MAPKi therapy. Placing genetically identical tumors in aged mice (52 weeks) significantly increased their response to anti-PD1 as compared with the same tumors in young mice (8 weeks). These data suggest that this increased response in aged patients occurs even in the absence of a more complex mutational landscape. Next, we found that young mice had a significantly higher population of regulatory T cells (Tregs), skewing the CD8
:Treg ratio. FOXP3 staining of human melanoma biopsies revealed similar increases in Tregs in young patients. Depletion of Tregs using anti-CD25 increased the response to anti-PD1 in young mice.
While there are obvious limitations to our study, including our inability to conduct a meta-analysis due to a lack of available data, and our inability to control for mutational burden, there is a remarkable consistency in these data from over 500 patients across 8 different institutes worldwide. These results stress the importance of considering age as a factor for immunotherapy response.
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To present an overview of a series of studies in which the clinical validity of the National Institutes of Health's Patient Reported Outcome Measurement Information System (NIH; PROMIS) measures was ...evaluated, by domain, across six clinical populations.
Approximately 1,500 individuals at baseline and 1,300 at follow-up completed PROMIS measures. The analyses reported in this issue were conducted post hoc, pooling data across six previous studies, and accommodating the different designs of the six, within-condition, parent studies. Changes in T-scores, standardized response means, and effect sizes were calculated in each study. When a parent study design allowed, known groups validity was calculated using a linear mixed model.
The results provide substantial support for the clinical validity of nine PROMIS measures in a range of chronic conditions.
The cross-condition focus of the analyses provided a unique and multifaceted perspective on how PROMIS measures function in “real-world” clinical settings and provides external anchors that can support comparative effectiveness research. The current body of clinical validity evidence for the nine PROMIS measures indicates the success of NIH PROMIS in developing measures that are effective across a range of chronic conditions.
Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%. We performed a ...genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.
The attractive physical and chemical properties of corundum lend to this material’s importance in both its natural and synthetic forms. However, much of the quantitative work performed on this ...material is plagued by unknown inaccuracy as non‐matrix‐matched reference materials are used. To conduct accurate quantitative analysis using SIMS, matrix‐specific relative sensitivity factors (RSFs) were determined for eighteen trace elements in corundum using dose‐verified ion implants. The RSF values ranged from 2.56 × 1022 to 3.29 × 1024 cm‐1 with total combined uncertainty values ranging from 7 to 10%. The RSF values, which are related to ionisation potentials, showed trends consistent with expectations for an insulating oxide. The developed values were applied to calibrate reference materials for LA‐ICP‐MS and to study other natural and synthetic corundum samples. A measurement reference material calibrated for Mg, Si, Ti, V, Fe and Ga produced consistent results over ten sessions in 4 years with relative standard deviations per trace element of 5% or less, confirming the repeatability of our process. A key finding was that calibrating LA‐ICP‐MS with NIST SRM 610 and 612 glasses to analyse corundum resulted in under‐reporting trace elements Be, Ti, V, Fe, Co, Ni and Ga compared with using matrix‐matched reference materials.
Key Points
SIMS RSF values for eighteen trace elements in corundum are presented.
Matrix‐matched reference materials were generated for Be, Mg, Si, Ti, V, Cr, Fe, Ni and Ga in corundum.
Matrix‐matched reference materials corrected for under‐reporting trace elements Be, Ti, V, Fe, Co, Ni and Ga using LA‐ICP‐MS calibrated with NIST SRM 610 and 612 glasses.
Communication problems (eg, dysphonia, dysfluency and language and articulation disorders), swallowing disorders (dysphagia and globus), cough and upper airway symptoms, resulting from functional ...neurological disorder (FND), are commonly encountered by speech and language professionals. However, there are few descriptions in the literature of the most effective practical management approaches. This consensus document aims to provide recommendations for assessment and intervention that are relevant to both adults and young people. An international panel of speech and language professionals with expertise in FND were approached to take part. Participants responded individually by email to a set of key questions regarding best practice for assessment and interventions. Next, a video conference was held in which participants discussed and debated the answers to these key questions, aiming to achieve consensus on each issue. Drafts of the collated consensus recommendations were circulated until consensus was achieved. FND should be diagnosed on the basis of positive clinical features. Speech and language therapy for FND should address illness beliefs, self-directed attention and abnormal movement patterns through a process of education, symptomatic treatment and cognitive behavioural therapy within a supportive therapeutic environment. We provide specific examples of these strategies for different symptoms. Speech and language professionals have a key role in the management of people with communication and related symptoms of FND. It is intended that these expert recommendations serve as both a practical toolkit and a starting point for further research into evidence-based treatments.
Total sleep time (TST), sleep efficiency (SE), and wake after sleep onset (WASO) as assessed by actigraphy gathered in 3 different modes were compared to polysomnography (PSG) measurements. Each mode ...was compared to PSG to determine which was more accurate. Associations of the difference in TST measurement with demographics and sleep characteristics were examined.
Observational study.
Community-based.
Sixty-eight women (mean age 81.9 years) from the latest visit of the Study of Osteoporotic Fractures who were concurrently measured with PSG and actigraphy.
N/A.
In-home 12-channel PSG was gathered along with actigraphy data in 3 modes: proportional integration mode (PIM), time above threshold (TAT) and zero crossings mode (ZCM). The PIM mode corresponded better to PSG, with a mean overestimation of TST of 17.9 min. For the PIM mode, the estimation of TST and SE by PSG and actigraphy significantly differed (P < 0.01), while the estimation of WASO was similar (P = 0.27). The intraclass correlation between the 2 procedures was moderate to high (PIM mode: TST 0.76; SE 0.61; WASO 0.58). On average, the PIM mode underestimated TST by 68 min for those who slept < or = 5 hr, overestimated TST by 31 min for those with SE < 70%, and underestimated TST by 24 min for self-reported poor sleepers (P < 0.05).
Sleep parameters from actigraphy corresponded reasonably well to PSG in this population, with the PIM mode of actigraphy correlating highest. Those with poor sleep quality had the largest measurement error between the 2 procedures.
Intrahepatic cholestasis of pregnancy, characterised by maternal pruritus and increased serum bile acid concentrations, is associated with increased rates of stillbirth, preterm birth, and neonatal ...unit admission. Ursodeoxycholic acid is widely used as a treatment without an adequate evidence base. We aimed to evaluate whether ursodeoxycholic acid reduces adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy.
We did a double-blind, multicentre, randomised placebo-controlled trial at 33 hospital maternity units in England and Wales. We recruited women with intrahepatic cholestasis of pregnancy, who were aged 18 years or older and with a gestational age between 20 weeks and 40 weeks and 6 days, with a singleton or twin pregnancy and no known lethal fetal anomaly. Participants were randomly assigned 1:1 to ursodeoxycholic acid or placebo, given as two oral tablets a day at an equivalent dose of 500 mg twice a day. The dose could be increased or decreased at the clinician's discretion, to a maximum of four tablets and a minimum of one tablet a day. We recommended that treatment should be continued from enrolment until the infant's birth. The primary outcome was a composite of perinatal death (in-utero fetal death after randomisation or known neonatal death up to 7 days after birth), preterm delivery (<37 weeks' gestation), or neonatal unit admission for at least 4 h (from birth until hospital discharge). Each infant was counted once within this composite. All analyses were done according to the intention-to-treat principle. The trial was prospectively registered with the ISRCTN registry, number 91918806.
Between Dec 23, 2015, and Aug 7, 2018, 605 women were enrolled and randomly allocated to receive ursodeoxycholic acid (n=305) or placebo (n=300). The primary outcome analysis included 304 women and 322 infants in the ursodeoxycholic acid group, and 300 women and 318 infants in the placebo group (consent to use data was withdrawn for 1 woman and 2 infants). The primary composite outcome occurred in 74 (23%) of 322 infants in the ursodeoxycholic acid group and 85 (27%) of 318 infants in the placebo group (adjusted risk ratio 0·85 95% CI 0·62–1·15). Two serious adverse events were reported in the ursodeoxycholic acid group and six serious adverse events were reported in the placebo group; no serious adverse events were regarded as being related to treatment.
Treatment with ursodeoxycholic acid does not reduce adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy. Therefore, its routine use for this condition should be reconsidered.
National Institute for Health Research Efficacy and Mechanism Evaluation Programme.
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